Progressive Decline in Interferon-γ Release is Associated with Cirrhosis Progression and Severity: A Prospective Preliminary Report

Cirrhosis progresses through distinct stages, with increasing severity and susceptibility to infections due to cirrhosis-associated immune dysfunction. Lymphocyte-based functional assays are considered the gold standard for assessing immune function, although none have been evaluated across different cirrhosis stages. We conducted a pilot study to assess whether performing interferon-γ (IFN-γ) release assays (IGRA), in response to a nonantigenic mitogen (phytohemagglutinin [PHA]), could help classify immune function and disease severity in 70 patients with cirrhosis awaiting liver transplantation. Disease severity ranged from chronic cirrhosis to acute-on-chronic liver failure. We measured IFN-γ release in response to PHA using a fresh heparinized whole-blood protocol. Progressive reduction in IFN-γ release correlated with increased disease severity parameters (with respect to total bilirubin level and number of organ failure instances). A moderate but highly significant correlation was observed between IFN-γ release and CD8⁺ T lymphocyte count (r=0.52, <i>P</i> <0.001). As a non-antigen-dependent mitogen, PHA enables the global assessment of lymphocyte IFN-γ-releasing capacity. Our whole-blood results suggest that PHA-IGRA testing may provide a useful parameter for characterizing immune dysfunction in patients with cirrhosis. These findings require further validation in larger cohorts to better define the clinical applicability of PHA-IGRA testing.